Eyes So Dry, Makes Me Want to Cry

by Alan R. Gaby, MD

As this issue of the Townsend Letter is focusing on eye conditions, it got me thinking about one of my favorite ophthalmological remedies: vitamin A eyedrops for the treatment of dry eye syndrome (also called sicca syndrome or keratoconjunctivitis sicca). In two uncontrolled trials, and 1 double-blind trial, application of eyedrops containing vitamin A resulted in improvement of dry eyes in most cases.^1–3 In another trial, vitamin A eyedrops were of similar efficacy to 0.05% cyclosporine eyedrops (Restasis) in improving tear production, blurred vision, and goblet cell density. The frequency of adverse events was lower with vitamin A eyedrops than with Restasis (4% vs. 10%).⁴ In addition, vitamin A eyedrops cost only about $10 per month, as compared with about $400 per month for Restasis.

However, there is one major problem with vitamin A eyedrops: you can’t get them anymore (unless you have them compounded by a pharmacist). The US Food and Drug Administration (FDA), after years of harassing the small company that was manufacturing these eyedrops, has now in effect shut them down. The story of the FDA versus vitamin A eyedrops is a classic example of how this government agency, whose job it is to protect the public, has instead harmed us.

When vitamin A eyedrops first entered the market a few decades ago, the product was called Vita-A drops. However, as told to me by the inventor of the product (now deceased), the FDA banned the sale of Vita-A drops on the grounds that the name constituted a de facto health claim. The FDA prohibits most health claims for natural products, and when “unapproved” claims are made, the agency considers the product to be a “misbranded drug,” which cannot legally be sold. According to the FDA’s way of thinking, there is no reason to put vitamin A in an eyedrop other than to treat an eye disorder. The public would know that a product named Vita-A eyedrops contains vitamin A, and they would assume that the vitamin was added to improve an eye disorder; ergo, the claim is in the name. After an extended legal battle and tens of thousands of dollars of legal fees, the FDA allowed the product to return to the market under a new name, Viva-Drops.

Several years passed, during which Viva-Drops were readily available and many people suffering from dry eyes were able to benefit. Then, the harassment started again. In 2011, the FDA sent a warning letter to Dakota Laboratories (the manufacturer of Viva-Drops), alleging that the company’s manufacturing procedures were in violation of the current good manufacturing practice (cGMP) regulations for Finished Pharmaceuticals. An example of one of the alleged violations was:

Your firm has not established appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile … For example … your aseptically manufactured products are filled into 15mL bottles; however, your process simulation studies (i.e., media fills) were conducted using 10mL and 12mL bottles which did not represent the products that would be manufactured. In your response, your firm states that two of the three media fills were successfully completed by the time the product was shipped to the customer. Your response is inadequate because you have not provided any assurances that your aseptic process was in a state of control during the manufacture of sterile drug products which were subsequently distributed.

Now, I’m not a microbiologist and I’m not an expert in the area of quality control, but while reading through the list of alleged violations, I could not help but think the FDA was purposely trying to create a scenario of “death by 1000 nitpicks.” The FDA could easily have shown Dakota Laboratories how better to comply with cGMP regulations, but instead the agency apparently chose to use those regulations as a blunt weapon.

On August 26, 2013, the US Justice Department filed suit on behalf of the FDA, seeking to prevent Dakota Laboratories from producing sterile eyedrops until it addressed the alleged cGMP violations. Had the suit gone to trial, the government would have had to prove by a preponderance of the evidence that Dakota Laboratories was violating the regulations. And it is noteworthy that the FDA had not received a single report of harm related to the use of any Dakota Laboratories product. However, in order to avoid another round of massive legal fees, the company agreed to a settlement, which essentially shut it down.

So, now Allergan is happily raking in a billion dollars a year from Restasis, while we the people no longer have access to a product that works just as well, causes fewer side effects, and is much less expensive. It doesn’t have to be this way.

Notes

1. Rengstorff RH et al. Topical antioxidant treatment for dry-eye disorders and contact lens-related complications. Afro-Asian J Ophthalmol. 1988;7:81–83.

2. Chandra DB et al. Topical vitamin A palmitate in dry eyes. Afro-Asian J Ophthalmol. 1988;7:74–80.

3. Westerhout D. Treatment of dry eyes with aqueous antioxidant eye drops. Contact Lens J. 1991;19:165–173.

4. Kim EC et al. A comparison of vitamin A and cyclosporine A 0.05% eye drops for treatment of dry eye syndrome. Am J Ophthalmol. 2009;147:206-213.e3.